rhBMP-2 Versus Autograft in Critical Size Tibial Defects

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by St. Louis University
Sponsor:
Collaborator:
Major Extremity Trauma Research Consortium
Information provided by (Responsible Party):
St. Louis University
ClinicalTrials.gov Identifier:
NCT00853489
First received: February 24, 2009
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

The purpose of our study is to evaluate the use of recombinant human bone morphogenetic protein 2 (RhBMP-2) as compared to standard ICBG in the treatment of severe open tibia fractures with a critical size bone defect (at least one centimeter in length compromising at least 50% of the circumference of the bone).


Condition Intervention Phase
Tibial Fractures
Device: recombinant bone morphogenetic protein 2
Procedure: Autogenous iliac crest bone graft
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: RhBMP-2 vs. Autograft for Critical Size Tibial Defects: A Multicenter Randomized Trial

Resource links provided by NLM:


Further study details as provided by St. Louis University:

Primary Outcome Measures:
  • Fracture healing (union) at 12 months [ Time Frame: op2 weeks, 6 weeks, 12 weeks, 18 weeks, 6 months and 12 months post op ] [ Designated as safety issue: Yes ]

    Union will be defined by meeting both of the following criteria:

    1. Radiographic union as defined by the RUST score, Radiographic evaluation will be assessed by blinded orthopaedic surgeons.
    2. Clinical union as defined by pain-free full weight bearing and lack of tenderness ,swelling and pain at the fracture site on palpation. Pain will be documented using the VAS at each visit. Swelling will be defined as the absence of skin wrinkling.


Secondary Outcome Measures:
  • Infection [ Time Frame: 2 weeks, 6 weeks, 12 weeks, 18 weeks, 6 months and 12 months post op. ] [ Designated as safety issue: Yes ]
    Infection will be assessed based on the CDC criteria for deep and superficial infection.

  • Functional Status [ Time Frame: 2 weeks, 6 weeks, 12 weeks, 18 weeks, 6 months and 12 months post op ] [ Designated as safety issue: No ]
    Function will be measured using the SF12 and the Short Form Musculoskeletal Assessment (SMFA)

  • Medical Cost [ Time Frame: 12 mos post op ] [ Designated as safety issue: No ]
    An economic evaluation will also be performed including the costs of iliac crest bone graft harvest and complications from the bone graft surgery and the cost of the Rh-BMP 2 and the biologic implant used in the treatment group.


Estimated Enrollment: 50
Study Start Date: August 2011
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: recombinant bone morphogenetic protein 2
The patient will receive rhBMP-2 plus allograft chips in the bone defect site. Intervention type: surgical
Device: recombinant bone morphogenetic protein 2
Patients will receive 1.50 mg/ml -12 mg of rhBMP-2 soaked on a absorbable collagen sponge (rhBMP-2/ACS) as an adjuvant to a freeze-dried cancellous allograft
Other Name: (rhBMP-2) (INFUSE)
Active Comparator: Autogenous iliac crest bone graft
Bone will be harvested from the iliac crest and placed in the bone defect.
Procedure: Autogenous iliac crest bone graft
Patients will undergo autogenous iliac crest bone graft surgery per the surgeon's usual practice.

Detailed Description:

Open tibia fractures have a 15% or higher rate of not healing. Those fractures which do not heal are typically treated with bone from the hip (iliac crest autograft; or ICBG). The use of ICBG bone with the treatment of delayed unions/non-unions with critical defect, although successful, has its drawbacks. The bone graft sources are limited and the procedure is associated with additional operating room time plus a second incision with increased risk of infection, post operative pain and increased hospital stay. The purpose of this study is to determine if Rh-BMP2, a new bone graft substitute, is at least as effective as using bone from the hip (autograft) to help promote healing of open, tibia (shin bone) fractures.

Research Questions:

Primary:

What is the relative effect of rhBMP-2 versus autogenous ICBG on rates of union in patients with critical size defects following tibial shaft fractures?

Null hypothesis #1: rhBMP-2 has the same union rate when used in critical-sized defects as does ICBG.

Secondary:

What is the relative effect of rhBMP-2 versus autogenous ICBG on infection rates in patients with nonunion or critical size defects following tibial shaft fractures?

Null hypothesis #2: The infection rate in open tibias with critical-sized defects treated with rhBMP-2 and autogenous ICBG are the same.

What is the economic impact of the use of Rh-BMP 2 for tibial fractures with critical sized defects?

Null hypothesis #3: There will be no difference in the economic cost of the treatment of critical sized defects using the RhBMP-2 versus iliac crest bone graft.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients 18-65 years old with an open tibia fracture involving diaphysis (if patient has a bilateral tibia fracture and both require a bone graft, then each will be randomized separately).
  • Tibia fractures with a circumferential bone defect of at least one centimeter in length compromising at least 50% of the circumference of the bone.
  • The definitive treatment of the tibia fracture must be with an intramedullary nail (may have temporary external fixation prior to IM nail placement).
  • Patients whose treatment plan includes placement of a bone graft between 6 to 16 weeks after their initial injury.
  • Patients who have no evidence of infection by clinical examination (defined as active infection at the operative site, purulent drainage from the fracture or evidence of active osteomyelitis at the time of bone graft).
  • Patients who are independent in living and ambulation prior to injury.
  • Patients who are English speaking.
  • Patients who are willing to provide consent and available for follow-up for at least 12 months following definitive surgical procedure.

Exclusion Criteria:

  • Patients who are pregnant or lactating.
  • Patients with known hypersensitivity to rhBMP-2 or bovine type I collagen.
  • Patients with a history of tumor, a resected or extant tumor, an active malignancy, or patients undergoing treatment for malignancy.
  • Patients who are skeletally immature (<18 years of age or no radiographic evidence of epiphyseal closure).
  • Patients with inadequate neurovascular status, e.g. high risk of amputation.
  • Patients with compartment syndrome of the affected limb.
  • Patients with immune deficiency or history of auto-immune disease,
  • Patients who have undergone treatment of any other investigational therapy within the month preceding implantation or planned within the 12 months following implantation.
  • Patients unable to return for required follow-up visits.
  • Patients who have medical co-morbidities that preclude treatment with a general anesthetic.
  • Patient who is pending incarceration or who is incarcerated.
  • Patients with an active infection at the operative site, purulent drainage from the fracture or evidence of active osteomyelitis at the time of bone grafting.
  • Patient has intraoperative positive gram stain or an elevated CRP after laboratory screening for infection.
  • Patient has segmental defects longer than 5cm in length.
  • Patients who have segmental defects that require more than 60 cc of bone graft.
  • Patients who require more than one large kit of rhBMP-2 at time of surgery.
  • Patient's anticipated treatment plan also includes the use of other procedures to promote fracture healing, e.g. ultrasound, magnetic field or electrical stimulation.
  • Patient's tibia fracture has been treated with additional fixation beyond the intramedullary nail, e.g. plates, wires or screws.
  • Patients who have pathological fractures; a known history of Paget's disease or known history of heterotropic calcification.
  • Patients with a Glasgow Coma Scale less than 15 (less than fully awake) at the time of informed consent.
  • Patients with previous hardware in place that prevents placement of an intramedullary nail for treatment of the tibial shaft fracture.
  • Patients with prior use of INFUSE.

If the patient is a female of child bearing potential:

  • Does she have a negative pregnancy test (administered within 72 hours prior to surgery)?
  • Has she agreed to use adequate contraception for a period of at least 1 year following implementation of rhBMP-2?
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853489

Contacts
Contact: Ellan MacKenzie, PhD 410-614-4025 emackenz@jhsph.edu
Contact: Lisa Reider, MS 410-502-3962 lsemanic@jhsph.edu

Locations
United States, California
UCSF Medical Center Recruiting
San Francisco, California, United States, 94115
Principal Investigator: Theodore Miclau, MD         
United States, Colorado
Denver Health and Hospital Authority Not yet recruiting
Denver, Colorado, United States, 80204
Principal Investigator: David J Hak, MD, MBA         
United States, Florida
University of Miami Ryder Trauma Center Recruiting
Miami, Florida, United States, 33101
Principal Investigator: Gregory Zych, MD         
Orlando Regional Medical Center Recruiting
Orlando, Florida, United States, 32806
Principal Investigator: Joshua Langford, MD         
Florida Orthopaedic Institute / Tampa General & St. Joseph's Hospitals Recruiting
Tampa, Florida, United States, 33606
Principal Investigator: Roy Sanders, MD         
United States, Indiana
Methodist Hospital Recruiting
Indianapolis, Indiana, United States, 46278
Principal Investigator: Todd McKinley, MD         
United States, Iowa
University of Iowa Hospitals Recruiting
Iowa City, Iowa, United States, 52242
Principal Investigator: J. Lawrence Marsh, MD         
United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Principal Investigator: Paul Tornetta, MD         
United States, Michigan
Orthopaedic Associates of Michigan, Spectrum Health Recruiting
Grand Rapids, Michigan, United States, 49503
Principal Investigator: Clifford B Jones, MD         
United States, Minnesota
Hennepin County Medical Center Recruiting
Minneapolis, Minnesota, United States, 55715
Principal Investigator: Andrew Schmidt, MD         
United States, Missouri
St. Louis Medical Center Recruiting
St. Louis, Missouri, United States, 63110
Principal Investigator: Lisa Cannada, MD         
United States, North Carolina
Carolinas Medical Center Recruiting
Charlotte, North Carolina, United States, 28232
Principal Investigator: Michael J. Bosse, MD         
United States, Ohio
MetroHealth Medical Center Recruiting
Cleveland, Ohio, United States, 44109
Principal Investigator: Heather Vallier, MD         
United States, Oklahoma
University of Oklahoma / OU Medical Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Principal Investigator: Dave Teague, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: William T. Obremskey, MD, MPH         
United States, Texas
Brooke Army Medical Center Not yet recruiting
Ft. Sam Houston, Texas, United States, 78234-6315
Principal Investigator: Daniel Stinner, MD         
United States, Washington
University of Washington / Harborview Medical Center Recruiting
Seattle, Washington, United States, 98104-2499
Principal Investigator: Bruce J. Sangeorzan, MD         
Sponsors and Collaborators
St. Louis University
Major Extremity Trauma Research Consortium
Investigators
Principal Investigator: Lisa Cannada, MD St. Louis Medical Center
Principal Investigator: Paul Tornetta, MD Boston Medical Center
  More Information

No publications provided

Responsible Party: St. Louis University
ClinicalTrials.gov Identifier: NCT00853489     History of Changes
Other Study ID Numbers: W81XWH-09-20108
Study First Received: February 24, 2009
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Louis University:
Open tibia fractures
rhBMP-2
critical size defects
bone grafting

Additional relevant MeSH terms:
Fractures, Bone
Tibial Fractures
Wounds and Injuries
Leg Injuries

ClinicalTrials.gov processed this record on July 26, 2014